A pair of recent studies, one from Germany and one from Australia, provides new insight into the development and treatment of skin cancers that could lead to significant improvements in the management of the disease.
In the first study, researchers from Monash University in Australia discovered that the developmental transcription factor Grhl3 is a “potent tumor suppressor” of squamous cell carcinoma (SCC) in mice. The researchers discovered that the transcription factor was missing in adult SCC tumor cells, which prevented the transmission of the signal that stops cancer cells from growing. While the research was initially conducted with patients who had SCC of the skin, the team also discovered eventually that Grhl3 is also lost in SCC that arises in other tissues, including head and neck cancers.
“Virtually every SCC tumor we looked at had almost undetectable levels of this particular gene, so its absence is a very profound driver of these cancers,” said department of medicine professor Stephen Jane, co-lead author of the study. “Our research indicates that drugs already in clinical trials for other cancers may actually be effective in treating SCC — they just need to be applied to skin or head and neck cancers. This means that a number of the usual hurdles in getting therapies to trial have already been cleared, so patients could be reaping the benefits of this research in under 5 years.”
In the second study from the University of Freiburg in Germany, the researchers performed tests with different chemotherapeutic agents to determine their efficacy in specific cancers and examine adverse reactions. The tests indicated that vemurafenib was most effective in melanoma tumor samples with the V600E BRAF gene mutation – it was 100 times more active in V600E-mutated melanomas compared to melanomas with no mutations – while vincristine was only effective in tumor samples that did not have a mutation in the BRAF gene. The researchers do note, however, that the majority of patients in the vemurafenib group developed resistance within a year.
“Up until now, we were not able to detect other correlations between chemosensitivity against cytotoxic or targeted agents and other mutations,” said study author Heinz-Herbert Fiebig, MD, PhD, associate professor of medical oncology at the University of Freiburg in Germany. “Our melanoma models will allow researchers to investigate and overcome the possible underlying resistance mechanisms — for example, by combining vemurafenib with other target-specific agents. In addition, other new targeted drugs are being studied in a systematic way.”
